The overall goals of the proposed research are to investigate a) the state of lipoprotein lipase activity in the heart, skeletal muscle and adipose tissue of rats with hypertriglyceridemia induced by carbohydrate feeding and diabetes mellitus; b) the possible existence of abnormalities in the plasma lipoproteins of these animals which would make them resistant to removal by the tissues and c) the factors which participate in the regulation of lipoprotein lipase activity in the rat myocardium. We plan to induce the accumulation of triglycerides in the plasma of rats by a) feeding them diets high in carbohydrate content and b) by injecting them with different doses of streptozotocin in order to produce diabetes of increasing severity. We will attempt to correlate the increases in plasma triglyceride concentration with changes in lipoprotein lipase activity in the tissues, and also compare the interaction of plasma lipoproteins, from normal and hypertriglyceridemic rats, with lipoprotein lipase. The factors which regulate lipoprotein lipase activity in tissues other than adipose tissue are not known. We plan to study the regulation of myocardial enzyme activity in vivo and in vitro, using the isolated perfused rat heart. With this system, which can be maintained metabolically active for long periods, we intend to examine the effects which serum from fed and starved rats have on the enzyme activity. We will also study the effects of heparin, glucose, insulin, glucagon, amino acids and cycloheximide in this system.